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Hyperinsulinemia provokes synchronous increases in central inflammation and beta-amyloid in normal adults
Fishel MA, Watson GS, Montine TJ, Wang Q, Green PS, Kulstad JJ, Cook DG, Peskind ER et al.. Archives of neurology, 2005-10-01
Topic: Brain proteins, microglia and lab models
Background Inflammation has been implicated as a pathogenetic factor in Alzheimer disease, possibly via effects on beta-amyloid (Abeta). Hyperinsulinemia induces inflammation and is a risk factor for Alzheimer disease. Thus, insulin abnormalities may contribute to Alzheimer disease pathophysiology through effects on the inflammatory network. Objectives To determine the effects of induced hyperinsulinemia with euglycemia on Abeta, transthyretin, and inflammatory markers and modulators in plasma and cerebrospinal fluid (CSF). Design Randomized crossover trial. Setting Veterans Affairs hospital clinical research unit. Participants Sixteen healthy adults ranging from 55 to 81 years of age (mean age, 68.2 years). Interventions On separate mornings, fasting participants received randomized infusions of saline or insulin (1.0 mU.kg(-1).min(-1)) with variable dextrose levels to maintain euglycemia, achieving plasma insulin levels typical of insulin resistance. Plasma and CSF were collected after an approximately 105-minute infusion. Main outcome measures Plasma and CSF levels of interleukin 1alpha, interleukin 1beta, interleukin 6, tumor necrosis factor alpha, F2-isoprostane (CSF only), Abeta, norepinephrine, transthyretin, and apolipoprotein E. Results Insulin increased CSF levels of F2-isoprostane and cytokines (both P Conclusion Moderate hyperinsulinemia can elevate inflammatory markers and Abeta42 in the periphery and the brain, thereby potentially increasing the risk of Alzheimer disease.
Key findings
- Results Insulin increased CSF levels of F2-isoprostane and cytokines (both P Conclusion Moderate hyperinsulinemia can elevate inflammatory markers and Abeta42 in the periphery and the brain, thereby potentially increasing the risk of Alzheimer disease.
Why it matters
In this small crossover study of 16 healthy adults, induced hyperinsulinemia increased inflammatory markers and Abeta42 in the periphery and the brain. The authors suggest this may potentially increase the risk of Alzheimer's disease, but the study did not test whether it actually causes dementia.
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Study details
- Evidence strengthHigh
How this study scored 51/100
Published in a peer-reviewed journal. Scored zero for study design, sample size, effect reported, studied in people and randomised / blinded because the record does not state it.
| Component | Points | Why |
|---|---|---|
| Journal tier | 7 / 10 | Tier 3 — peer-reviewed journal (Archives of neurology) |
| Journal's citation record | 3 / 4 | Archives of Neurology: journal h-index 353 (OpenAlex, 2026-10-29) |
| Study design | 0 / 12 | No study design recorded — scores zero, not guessed (not stated in the record — scored 0) |
| Strength of evidence | 5 / 5 | Rated “high” in our summary |
| Peer-review validation | 10 / 10 | Peer-reviewed. Published as an article in a named peer-reviewed journal. |
| How recent | 1 / 5 | 2005 — older than 20 years, still counted |
| Sample size | 0 / 4 | Participant count not stated — scores zero (not stated in the record — scored 0) |
| Effect reported | 0 / 3 | No effect size reported — scores zero (not stated in the record — scored 0) |
| Studied in people | 0 / 3 | Not stated whether this was studied in people — scores zero (not stated in the record — scored 0) |
| Randomised / blinded | 0 / 2 | No randomisation or blinding stated — scores zero (not stated in the record — scored 0) |
| Times cited | 5 / 7 | Cited 220 times (OpenAlex, 2026-10-10) |
| Citations per year | 3 / 5 | 9.6 citations a year over 23 year(s) since 2005 |
| Impact for its field and year | 4 / 6 | Cited 8.2× the average for papers of its field and year (OpenAlex FWCI) |
| Cited by studies here | 2 / 6 | Cited by 8 other studies in this library |
| Still being cited | 2 / 4 | Cited 22 times in 2024–2026 (2026 still in progress; OpenAlex) |
| Senior author's track record | 4 / 4 | Last-listed author Suzanne Craft: h-index 103 (OpenAlex, whole career) |
| Institution's track record | 3 / 3 | University of Washington: institution h-index 3,540 (OpenAlex) |
| Multi-centre collaboration | 0 / 3 | OpenAlex lists 1 institution(s) in 1 country — scores zero (affiliation lists can be incomplete) |
| Indexed in PubMed | 2 / 2 | Indexed in PubMed (PMID 16216936) |
| Free to read | 0 / 2 | Behind a paywall — scores zero |
| Total | 51 / 100 | — |
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Read the original
May need a subscription Unpaywall, Europe PMC and OpenAlex found no free copy of the full text (checked 10 Oct 2026), so the publisher may charge for it. The PubMed abstract is free.
Cite this study APA, Vancouver, BibTeX · download .bib or .ris
Built from the record alzhub holds for this paper, not looked up. Volume, issue and page numbers are not held in the record. The record's author list ends in “et al.”, so not every author is named. Check the citation against the original before you use it.
APA 7th
Fishel, M. A., Watson, G. S., Montine, T. J., Wang, Q., Green, P. S., Kulstad, J. J., et al. (2005). Hyperinsulinemia provokes synchronous increases in central inflammation and beta-amyloid in normal adults. Archives of neurology. https://doi.org/10.1001/archneur.62.10.noc50112
Vancouver
Fishel MA, Watson GS, Montine TJ, Wang Q, Green PS, Kulstad JJ, et al. Hyperinsulinemia provokes synchronous increases in central inflammation and beta-amyloid in normal adults. Archives of neurology. 2005. doi:10.1001/archneur.62.10.noc50112. PMID: 16216936.
BibTeX
@article{fishel2005-16216936,
author = {Fishel, M. A. and Watson, G. S. and Montine, T. J. and Wang, Q. and Green, P. S. and Kulstad, J. J. and Cook, D. G. and Peskind, E. R. and others},
title = {{Hyperinsulinemia provokes synchronous increases in central inflammation and beta-amyloid in normal adults}},
journal = {Archives of neurology},
year = {2005},
doi = {10.1001/archneur.62.10.noc50112},
pmid = {16216936},
url = {https://doi.org/10.1001/archneur.62.10.noc50112}
}
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